反応 #89635

反応方程式

(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

HCl

acetic acid

→

(3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

収率 79.0%

溶媒

water

water

反応条件

後処理

1. 1
   その他capped
2. 2
   温度cooled to room temperature
3. 3
   抽出extracted with methylene chloride (20 mL)
4. 4
   濃縮concentrated
5. 5
   workup.ADDITIONThe residue was treated with water (20 mL)
6. 6
   濃縮concentrated three times
7. 7
   その他to remove excess HCl
8. 8
   workup.DISSOLUTIONdissolved in water (40 mL)
9. 9
   workup.ADDITIONtreated with DOWEX® 550A-OH resin (3 g) which
10. 10
    洗浄had been rinsed with methanol
11. 11
    workup.STIRRINGThe mixture was stirred for 40 min
12. 12
    ろ過filtered
13. 13
    洗浄the resin washed successively with water, methanol, methylene chloride, water, methanol, and methylene chloride
14. 14
    workup.STIRRINGThe resin was then stirred four times with 1N HCl (15 mL)
15. 15
    ろ過filtered
16. 16
    濃縮the combined filtrates were concentrated
17. 17
    workup.ADDITIONThe residue was treated with water (20 mL)
18. 18
    濃縮concentrated three times
19. 19
    その他to remove excess HCl
20. 20
    workup.DISSOLUTIONdissolved in 1.5-2.0 mL water
21. 21
    その他subjected to HPLC gradient purification
22. 22
    濃縮The appropriate fractions were concentrated
23. 23
    workup.ADDITIONtreated three times with 1 N HCl (10 mL)
24. 24
    濃縮concentrated
25. 25
    workup.ADDITIONtreated three times with water (10 mL)
26. 26
    濃縮concentrated
27. 27
    workup.DISSOLUTIONdissolved in water (10 mL)
28. 28
    温度frozen
29. 29
    workup.WAITlyophilized overnight

実験手順

A solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (198 mg, 0.5 mmol) in 2:1:1 concentrated HCl:glacial acetic acid:water (8 mL) in a pressure bottle was stirred for 2 h at 60° C., then capped and stirred for 18 h at 130° C., cooled to room temperature, and uncapped. The solution was diluted with water (20 mL), then extracted with methylene chloride (20 mL) and concentrated. The residue was treated with water (20 mL) and concentrated three times to remove excess HCl, then dissolved in water (40 mL) and treated with DOWEX® 550A-OH resin (3 g) which had been rinsed with methanol. The mixture was stirred for 40 min, then filtered and the resin washed successively with water, methanol, methylene chloride, water, methanol, and methylene chloride. The resin was then stirred four times with 1N HCl (15 mL) and filtered, and the combined filtrates were concentrated. The residue was treated with water (20 mL) and concentrated three times to remove excess HCl, then dissolved in 1.5-2.0 mL water and subjected to HPLC gradient purification as follows: 0-25% B with A=0.1% trifluoroacetic acid/water and B=0.1% trifluoroacetic acid/acetonitrile. The appropriate fractions were concentrated, treated three times with 1 N HCl (10 mL) and concentrated, treated three times with water (10 mL) and concentrated, then dissolved in water (10 mL), frozen, and lyophilized overnight to afford (3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (114 mg, 79%) as a pale amber glass. NMR (D2O) δ 3.90 (d, J=13 Hz, 1 H), 3.71 (dd, J111.5 Hz, J2=8.5 Hz, 1 H), 3.46 (d, J=13 Hz, 1 H), 3.21 (t, J=12 Hz, 1 H), 2.50-2.65 (m, 1 H), 1.5-1.65 (m, 1 H), 1.10-1.40 (m, 3 H), 0.60-0.75 (m, 2 H). MS (m+1): 217.3; MS (m−H2O+1): 199.1.

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